Research Papers:
Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma by restoring aberrantly reduced profilin 1
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Abstract
Kaikai Shen1,*, Zhichao Xi1,*, Jianling Xie4, Hua Wang5, Chanlu Xie6, C.Soon Lee6,7, Paul Fahey6, Qihan Dong6,7,8, Hongxi Xu1,2,3
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
2Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital/ Shanghai University of T.C.M, Shanghai, China
3Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, China
4Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, Australia
5Stanley Ho Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China
6School of Science and Health, The University of Western Sydney, Sydney, Australia
7Central Clinical School and Bosch Institute, The University of Sydney, Sydney, Australia
8Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
*These authors contributed equally to this work
Correspondence to:
Hongxi Xu, email: [email protected]
Qihan Dong, email: [email protected]
Keywords: hepatocellular carcinoma, cancer metastasis, Guttiferone K, profilin1, actin
Received: November 20, 2015 Accepted: July 18, 2016 Published: August 01, 2016
ABSTRACT
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over-expression of PFN1 mimicked the effect of GUTK on HCC cell motility and metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over-expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased F-actin levels and the expression of proteins involved in actin nucleation, branching and polymerization. Moreover, a reduction of PFN1 protein levels was common in advanced human HCC and associated with poor survival rate. In conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells mainly by restoration of aberrantly reduced PFN1 protein expression.
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PII: 10992